Cataracts are the foremost cause of blindness in the world and currently can be treated only by surgical removal. Surgery, although easily available and safely performed in the U.S., is not easily available nor safely performed in many undeveloped regions in the world like Asia, Africa, the Middle East and South America. Hence we are studying ways to treat cataract using medical (non surgical) treatment. [unreadable] One principal theory on the cause of cataracts is that the crystallin proteins inside the lens clump together to form high molecular weight "aggregates" that scatter light and cause clouding of the lens. This can be due to overwhelming external stresses or failure of internal protective systems to work. We are working on a new technology that will help us find out what happens to the lens tissues that may lead to cataracts, and therefore help us find a cure for cataracts. It will also help determine if new potential anti cataract drugs do work in patients, since it can detect progression or regression of the cataract early on. [unreadable] This technology is based on Dynamic Light Scattering or DLS, that can detect molecular interactions, including lens crystallin protein interactions that occur in the lens of a living patient. This technology sorts out particle size, shape and interactions based on the brownian movement of these particles inside the living eye. [unreadable] First using the new DLS probe on animal models of cataract, we indeed found lens protein aggregation as a cataract initially develops. These studies showed the DLS's potential to detect the earliest changes occurring in cataract, at the stage where anti cataract treatment would theoretically be most effective in reversing, delaying or preventing cataracts. [unreadable] In collaboration with Drs. Ansari and Suh of NASA's John Glenn Center in Cleveland, Ohio, we developed a new miniaturized clinical version of this device for use on patients, modifying it using feedback from our patients in a preliminary study. We mounted the DLS probe successfully on the Keratoscope, a clinical device used by cornea surgeons to map the cornea, which has a 3-D aiming system to enhance repeatability. [unreadable] We then conducted a pilot study on 15 normal human volunteers (Phase 1) to test the safety, usefulness and reproducibility of this instrument for quantitating lens changes, and found good reproducibility. We also derived the mean log particle size (derived from particle size distribution) to be used as the preferred parameter to use for our data. [unreadable] In the current Phase 2 of this project, we successfully recruited and studied 250 patients in a cross sectional study to determine the clinical changes in the human lens in vivo due to aging (age related changes), as well as molecular changes found in the three main types of cataracts (nuclear, cortical and PSC). Each patient underwent a complete comprehensive eye examination, cataract clinical grading, photography of the cataract (followed by grading of the photograph by a Reading Center), and finally testing with the Clinical DLS device. All patients in this NEI-IRB approved study gave their full informed consent.[unreadable] We found that with normal aging, there is a slow but continuous loss of the small protein group, and continuous increase high molecular weight lens proteins. During cataract formation, we observed first a slow decrease, followed by loss of the low molecular weight proteins. Concurrently, there was a dramatic increase in high molecular weight proteins, so that in a cataract (such as an AREDS Clinical Stage 2.5 nuclear cataract), all the lens proteins formed a large molecular weight grouop or even a single peak in many cases. In some cortical and posterior subcapsular cataracts, there are marked molecular changes in the lens nucleus even when the nucleus remains clear and does not seem to be affected. [unreadable] It worth pointing out that previously, these in vivo, non invasive lens aging and cataract studies were not even possible because we had no way to detect and measure these early lens and cataract changes in the molecular level. This new technology offers a new, sensitive and precise method to study conditions and medications that can either cause cataract or prevent cataract. [unreadable] Statistical analysis of the data showed excellent correlation between DLS data and Clinical and photographic Lens Grading data, demonstrating the validity of the system in detecting and measuring cataractous change. The data also showed good reproducibility (less than 5% error). [unreadable] This study shows that the DLS method can detect and measure the severity of clouding of the lens (cataract) objectively, making it useful in field as well as remote studies such as in monitoring astronauts for cataract in outer space. The development of this technique will help us conduct future clinical cataract studies of all sorts, with great sensitivity and accuracy. This technology will help us to better understand the underlying causes of cataracts and help us develop and test new treatments to delay, reverse or prevent cataract formation such as the National Eye Institute's Tempol H eye drops which was recently developed.